9s41

Publication Abstract from PubMed

AMPA receptors (AMPARs) are multimodal transducers of glutamatergic signals throughout the brain. Their diversity is exemplified in the cerebellum; at afferent synapses, AMPARs mediate high-frequency excitation, whereas in Bergmann glia (BG) they support calcium transients that modulate synaptic transmission. This spectrum arises from different combinations of core subunits (GluA1-4), auxiliary proteins, and post-transcriptional modifications. Here, using mass-spectrometry, cryo-EM, and electrophysiology, we characterize major cerebellar AMPARs in pig: calcium-impermeable GluA2/A4 heteromers with four TARP subunits, mainly neuronal in origin, and BG-specific calcium-permeable GluA1/A4 heteromers containing two Type-2 TARPs. We also showed that GluA4 receptors consistently exhibit compact N-terminal domains that promote their synaptic delivery. Our study defines the organizational principles of mammalian cerebellar AMPAR complexes and reveals how different receptor subtypes support cell-type specific functions.

Structure and organization of AMPA receptor-TARP complexes in the mammalian cerebellum.,Scrutton AM, Sengupta N, Ivica J, Stockwell I, Peak-Chew S, Singh B, Suzuki K, Chang VT, McLaughlin SH, Krieger JM, Aricescu AR, Greger IH Science. 2025 Dec 11:eaeb3577. doi: 10.1126/science.aeb3577. PMID:41379938^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.